Proteomic Approach Toward Molecular Backgrounds of Drug Resistance of Osteosarcoma Cells in Spheroid Culture System.

Proteomic approach toward molecular backgrounds of drug resistance of osteosarcoma cells in spheroid culture system.

Proteomics. 2013 May 28;
Arai K, Sakamoto R, Kubota D, Kondo T

Chemoresistance is one of the most critical prognostic factors in osteosarcoma, and elucidation of the molecular backgrounds of chemoresistance may lead to better clinical outcomes. Spheroid cells resemble in vivo cells and are considered an in vitro model for the drug discovery. We found that spheroid cells displayed more chemoresistance than conventional monolayer cells across 11 osteosarcoma cell lines. To investigate the molecular mechanisms underlying the resistance to chemotherapy, we examined the proteomic differences between the monolayer and spheroid cells by 2D-DIGE. Of the 4762 protein species observed, we further investigated 435 species with annotated mass spectra in the public proteome database, Genome Medicine Database of Japan Proteomics. Among the 435 protein species, we found that 17 species exhibited expression level differences when the cells formed spheroids in more than 5 cell lines and 4 species out of these 17 were associated with spheroid-formation associated resistance to doxorubicin. We confirmed the up-regulation of cathepsin D in spheroid cells by western blotting. Cathepsin D has been implicated in chemoresistance of various malignancies but has not previously been implemented in osteosarcoma. Our study suggested that the spheroid system may be a useful tool to reveal the molecular backgrounds of chemoresistance in osteosarcoma. This article is protected by copyright. All rights reserved. HubMed – drug


Synthesis of an (11) C-Labeled Antiprion GN8 Derivative and Evaluation of Its Brain Uptake by Positron Emission Tomography.

ChemMedChem. 2013 May 24;
Kimura T, Sako T, Siqin , Hosokawa-Muto J, Cui YL, Wada Y, Kataoka Y, Doi H, Sakaguchi S, Suzuki M, Watanabe Y, Kuwata K

A radiolabeled PET! A (11) C-labeled derivative of N,N’-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl) acetamide] (GN8), an antiprion agent currently under development, was synthesized by palladium-catalyzed rapid methylation of aryltributylstannane and assessed for brain penetration and organ distribution in rats by positron emission tomography (PET). HubMed – drug


Non-Invasive Synergistic Treatment of Brain Tumors by Targeted Chemotherapeutic Delivery and Amplified Focused Ultrasound-Hyperthermia Using Magnetic Nanographene Oxide.

Adv Mater. 2013 May 27;
Yang HW, Hua MY, Hwang TL, Lin KJ, Huang CY, Tsai RY, Ma CC, Hsu PH, Wey SP, Hsu PW, Chen PY, Huang YC, Lu YJ, Yen TC, Feng LY, Lin CW, Liu HL, Wei KC

The combination of chemo-thermal therapy is the best strategy to ablate tumors, but how to effectively heat deep tumor tissues without side-damage is a challenge. Here, a systemically delivered nanocarrier is designed with multiple advantages, including superior heat absorption, highly efficient hyperthermia, high drug capacity, specific targeting ability, and molecular imaging, to achieve both high antitumor efficacy and effective amplification of hyperthermia with minimal side effects. HubMed – drug


Engineering Polymeric Microparticles as Theranostic Carriers for Selective Delivery and Cancer Therapy.

Adv Healthc Mater. 2013 May 28;
Win KY, Ye E, Teng CP, Jiang S, Han MY

Multifunctional polymeric nano- and microparticles are engineered as theranostic carriers and their selective size-dependent cellular uptake is demonstrated. It is found that effective uptake and accumulation of nanoparticles occurs in both normal and cancer cells, whereas, that of microparticles occurs in cancer cells but not in normal cells, allowing cancer cells to be specifically targeted for local drug delivery. HubMed – drug